POS0657 LONG-TERM SAFETY OF UPADACITINIB IN PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS, AND NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS UP TO 5 YEARS
Authors: G. R. Burmester, J. Stigler, A. Rubbert-Roth, Y. Tanaka, V. F. Azevedo, D. Coombs, R. Mccaskill, R. Lippe, P. Wung, L. S. Gensler
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The efficacy and safety of upadacitinib (UPA), an oral JAK inhibitor, has been demonstrated in phase 3 trials for PsA, <sup>[1,2]</sup> AS, <sup>[3,4]</sup> and non-radiographic axial spondyloarthritis (nr-axSpA) <sup>[5]</sup>. <h3>Objectives</h3> To provide a safety update for UPA across PsA, AS, nr-axSpA, and pooled axSpA from the SELECT program. <h3>Methods</h3> Safety data (cut-off: 15 Aug 2022) from 5 UPA trials in PsA (2), AS (2), and nr-axSpA (1) were compiled. Treatment-emergent adverse events (TEAEs; onset on or after first dose and ≤30 days for UPA 15 mg [UPA15], or ≤70 days for adalimumab [ADA], after last dose) were summarized for PsA (pooled UPA15 and ADA [1 study only]), AS (pooled UPA15), nr-axSpA (UPA15), and pooled axSpA (pooled UPA15 from AS and nr-axSpA trials). TEAEs are reported as exposure-adjusted event rates (events/100 patient-years [E/100 PY]). Age-gender adjusted standard incidence ratios (SIRs) using the SEER database and standardized mortality ratios (SMRs) were calculated. <h3>Results</h3> A total of 1789 patients (PsA, n=907; AS, n=596; nr-axSpA, n=286) received ≥1 dose of UPA15, totaling ~3690 PY of exposure (<b>Table 1</b>). Overall AEs and serious AEs were highest in PsA, and numerically higher with UPA15 vs ADA; rates were generally similar between AS and nr-axSpA. AEs leading to discontinuation were generally similar across treatment groups and diseases and were numerically lowest in AS. Rates of malignancy excluding non-melanoma skin cancer (NMSC), MACE, and VTE were similar between UPA15 and ADA in PsA and were generally similar across diseases (<b>Figure 1</b>). In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and NMSC were observed with UPA15 vs ADA. The SIR (95% CI) for malignancy excluding NMSC with UPA15 was 0.94 (0.54-1.53) in PsA and 0.58 (0.12-1.69) in pooled axSpA; SIRs for AS (1 case) and nr-axSpA (2 cases) were not calculated separately due to low events. In PsA, the SMR (95% CI) with UPA15 was 0.71 (0.40-1.18), and 0.33 (0.13-0.69) with COVID-19 deaths excluded, suggesting no increased risk of death vs the general population. SMRs were not calculated for AS, nr-axSpA, or pooled axSpA due to low events. Data from this analysis should be interpreted with caution, as it was not enriched for AEs and duration of exposure was more limited for AS and nr-axSpA. <h3>Conclusion</h3> Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with UPA15 vs ADA in PsA; slightly elevated rates for most of these TEAEs were also observed with UPA15 in PsA vs axSpA. Apart from these differences, UPA15 demonstrated a generally consistent safety profile across disease states, with no new safety signals identified from previous reports. <h3>References</h3> [1]McInnes et al. <i>N Eng J Med</i>. 2021;384(13):1227-39. [2]Mease et al. <i>Ann Rheum Dis</i>. 2021;80(3):312-20. [3]van der Heijde et al. <i>Lancet</i>. 2019;394(10214):2108-17. [4]van der Heijde et al. <i>Ann Rheum Dis</i>. 2022;81(11):1515-23. [5]Deodhar et al. <i>Lancet</i>. 2022;400(10349):369-79. <h3>Acknowledgements</h3> AbbVie funded these studies (NCT03104400, NCT03104374, NCT03178487, NCT04169373) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie. <h3>Disclosure of Interests</h3> Gerd Rüdiger Burmester Speakers bureau: AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche, and UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche, and UCB, Jayne Stigler Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Andrea Rubbert-Roth Speakers bureau: AbbVie, Amgen, BMS, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi, Consultant of: AbbVie, Amgen, BMS, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Grant/research support from: AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda, Valderilio F Azevedo Speakers bureau: AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, GSK, Janssen, Novartis, Organon, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, GSK, Janssen, Novartis, Organon, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, GSK, Janssen, Novartis, Organon, Pfizer, and UCB, Derek Coombs Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Reva McCaskill Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Ralph Lippe Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: AbbVie, Lianne S. Gensler Consultant of: AbbVie, Fresenius Kabi, Gilead, Janssen, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from: Novartis and UCB Pharma.